PROJECT SUMMARY/ABSTRACT Recent work suggests that functional T1? provides a novel imaging technique to study brain function. This signal has been to exist in human and animal studies of the visual cortex. This technique has been shown to be separate from the hemodynamic response typically used to assess brain function using MR imaging. Initial work has shown that this signal responds faster than arterial and venous vascular signals measured using ASL and BOLD imaging respectively. In addition, the T1? signal has been shown to be sensitive to metabolism (glucose, glutamate, and pH) as well as neural currents. Finally, we have shown that the functional T1? signal was sensitive to changes in panic disorder not evident using BOLD imaging as well as shows a decoupling from the BOLD signal in bipolar disorder. These findings highlight the unique capabilities of this new functional imaging technique, which may provide new insight into psychiatric and neurological disorders. However, a number of gaps exist in our current understanding of the functional T1? signal, which this proposal aims to address. The aims of this project include: 1) Determine the relationship between functional T1? responses and local metabolites and neural currents using implanted biosensors in animal models; 2) Enhance spatial coverage and temporal sampling of functional T1? imaging using multi-band and compressed-sensing; 3) Determine the temporal and spatial response functions of T1? relative to BOLD and ASL; and 4) Evaluate the stability, reliability, and accuracy of functional T1? mapping. As part of these specific aims, we will evaluate techniques to eliminate the intravascular signal from the measurements and define a canonical impulse response function that can be used in the analysis of future functional T1? imaging studies. Finally, the reliability analysis proposed in Aim 4 will determine the ability of functional T1? mapping to be adopted by other groups and extend the technique to paradigms outside of the visual cortex. The proposed study will allow us to interpret the functional changes between patient populations by understanding the source of the functional T1? signal. The understanding of the signal source will also highlight many other psychiatric and neurological disorders where this functional imaging technique can be applied.